Pharmacokinetics of dietary kaempferol and its metabolite 4-hydroxyphenylacetic acid in rats

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Autor:innen
Zabela, Volha
Sampath, Chethan
Oufir, Mouhssin
Moradi-Afrapoli, Fahimeh
Butterweck, Veronika
Hamburger, Matthias
Autor:in (Körperschaft)
Publikationsdatum
12/2016
Typ der Arbeit
Studiengang
Sammlung
Institut für Medizintechnik und Medizininformatik
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Typ
01A - Beitrag in wissenschaftlicher Zeitschrift
Herausgeber:innen
Herausgeber:in (Körperschaft)
Betreuer:in
Ãœbergeordnetes Werk
Fitoterapia
Themenheft
DOI
https://doi.org/10.1016/j.fitote.2016.10.008
URI
http://hdl.handle.net/11654/23719
Link
http://www.sciencedirect.com/science/article/pii/S0367326X16306074
Reihe / Serie
Jahrgang / Band
115
Ausgabe / Nummer
Seiten / Dauer
189-197
Patentnummer
Verlag / Herausgebende Institution
Elsevier
Verlagsort / Veranstaltungsort
Auflage
Version
Programmiersprache
Abtretungsempfänger:in
Praxispartner:in/Auftraggeber:in
Zusammenfassung
SCOPE: Kaempferol is a major flavonoid in the human diet and in medicinal plants. The compound exerts anxiolytic activity when administered orally in mice, while no behavioural changes were observed upon intraperitoneal administration, or upon oral administration in gut sterilized animals. 4-Hydroxyphenylacetic acid (4-HPAA), which possesses anxiolytic effects when administered intraperitoneally, is a major intestinal metabolite of kaempferol. Pharmacokinetic properties of the compounds are currently not clear. METHODS AND RESULTS: UHPLC-MS/MS methods were validated to support pharmacokinetic studies of kaempferol and 4-HPAA in rats. Non-compartmental and compartmental analyses were performed. After intravenous administration, kaempferol followed a one-compartment model, with a rapid clearance (4.40-6.44l/h/kg) and an extremely short half-life of 2.93-3.79min. After oral gavage it was not possible to obtain full plasma concentration-time profiles of kaempferol. Pharmacokinetics of 4-HPAA was characterized by a two-compartment model, consisting of a quick distribution phase (half-life 3.04-6.20min) followed by a fast elimination phase (half-life 19.3-21.1min). CONCLUSION: Plasma exposure of kaempferol is limited by poor oral bioavailability and extensive metabolism. Both compounds are rapidly eliminated, so that effective concentrations at the site of action do not appear to be reached. At present, it is not clear how the anxiolytic-like effects reported for the compounds can be explained.
Schlagwörter
4-HPAA, Kaempferol, Pharmacokinetics, UHPLC-MS/MS
Fachgebiet (DDC)
Projekt
Veranstaltung
Startdatum der Ausstellung
Enddatum der Ausstellung
Startdatum der Konferenz
Enddatum der Konferenz
Datum der letzten Prüfung
ISBN
ISSN
1873-6971
0367-326X
Sprache
Englisch
Während FHNW Zugehörigkeit erstellt
Ja
Publikationsstatus
Veröffentlicht
Begutachtung
Peer-Review der ganzen Publikation
Open Access-Status
Lizenz
Zitation
ZABELA, Volha, Chethan SAMPATH, Mouhssin OUFIR, Fahimeh MORADI-AFRAPOLI, Veronika BUTTERWECK und Matthias HAMBURGER, 2016. Pharmacokinetics of dietary kaempferol and its metabolite 4-hydroxyphenylacetic acid in rats. Fitoterapia. Dezember 2016. Bd. 115, S. 189–197. DOI 10.1016/j.fitote.2016.10.008. Verfügbar unter: http://hdl.handle.net/11654/23719
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